Short-sighted virus evolution and a germline hypothesis for chronic viral infections

This work was funded by The Wellcome Trust and The Royal Society grant numbers wtvm055984 (KAL) and 107653/Z/15/Z (JG), The Natural Environment Research Council grant number NE/K009524/1 (AG), and The European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant number 614725-PATHPHYLODYN (OGP).With extremely short generation times and high mutability, many viruses can rapidly evolve and adapt to changing environments. This ability is generally beneficial to viruses as it allows them to evade host immune responses, evolve new behaviours, and exploit ecological niches. However, natural selection typically generates adaptation in response to the immediate selection pressures that a virus experiences in its current host. Consequently, we argue that some viruses, particularly those characterised by long durations of infection and ongoing replication, may be susceptible to short-sighted evolution, whereby a virus’ adaptation to its current host will be detrimental to its onward transmission within the host population. Here we outline the concept of short-sighted viral evolution and provide examples of how it may negatively impact viral transmission among hosts. We also propose that viruses that are vulnerable to short-sighted evolution may exhibit strategies that minimise its effects. We speculate on the various mechanisms by which this may be achieved, including viral life history strategies that result in low rates of within-host evolution, or the establishment of a ‘germline’ lineage of viruses that avoids short-sighted evolution. These concepts provide a new perspective on the way in which some viruses have been able to establish and maintain global pandemics.Publisher PDFPeer reviewe

Number of HIV-1 founder variants is determined by the recency of the source partner infection

During sexual transmission, the high genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection. Understanding the drivers of this bottleneck is crucial to developing effective infection control strategies. Little is known about the importance of the source partner during this bottleneck. To test the hypothesis that the source partner affects the number of HIV founder variants, we developed a phylodynamic model calibrated using genetic and epidemiological data on all existing transmission pairs for whom the direction of transmission and the infection stage of the source partner are known. Our results suggest that acquiring infection from someone in the acute (early) stage of infection increases the risk of multiple-founder variant transmission compared with acquiring infection from someone in the chronic (later) stage of infection. This study provides the first direct test of source partner characteristics to explain the low frequency of multiple-founder strain infections

Changes in cardiac-driven perivascular fluid movement around the MCA in a pharmacological model of acute hypertension detected with non-invasive MRI

Perivascular spaces mediate a complex interaction between cerebrospinal fluid and brain tissue that may be an important pathway for solute waste clearance. Their structural or functional derangement may contribute to the development of age-related neurogenerative conditions. Here, we employed a non-invasive low b-value diffusion-weighted ECG-gated MRI method to capture perivascular fluid movement around the middle cerebral artery of the anaesthetised rat brain. Using this method, we show that such MRI estimates of perivascular fluid movement directionality are highly sensitive to the cardiac cycle. We then show that these measures of fluid movement directionality are decreased in the angiotensin-II pharmacological model of acute hypertension, with an associated dampening of vessel pulsatility. This translational MRI method may, therefore, be useful to monitor derangement of perivascular fluid movement associated with cardiovascular pathologies, such as hypertension, in order to further our understanding of perivascular function in neurology

Coordination chemistry of amide-functionalised tetraazamacrocycles: structural, relaxometric and cytotoxicity studies

Three different tetraazamacrocyclic ligands containing four amide substituents that feature groups (namely allyl, styryl and propargyl groups) suitable for polymerisation have been synthesised. Gadolinium(III) complexes of these three ligands have been prepared as potential monomers for the synthesis of polymeric MRI contrast agents. To assess the potential of these monomers as MRI contrast agents, their relaxation enhancement properties and cytotoxicity have been determined. A europium(III) complex of one of these ligands (with propargyl substituents) is also presented together with its PARACEST properties. In addition, to gain further insight into the coordination chemistry of the tetra-propargyl substituted ligand, the corresponding zinc(II) and cadmium(II) complexes have been prepared. The X-ray crystal structures of the tetra-propargyl ligand and its corresponding gadolinium(III), zinc(II) and cadmium(II) complexes are also presented

Grey matter abnormalties in first episode schizophrenia and affective psychosis

Background: Grey matter and other structural brain abnormalities are consistently reported in first-onset schizophrenia, but less is known about the extent of neuroanatomical changes in first-onset affective psychosis. Aims: To determine which brain abnormalities are specific to (a) schizophrenia and (b) affective psychosis. Method: We obtained dual-echo (proton density/T2-weighted) MR images and carried out voxel-based analysis on the images of 73 first-episode psychosis patients (schizophrenia=44, affective psychosis=29) and 58 healthy controls. Results: Both patients with schizophrenia and patients with affective psychosis had enlarged lateral and third ventricle volumes. Regional cortical grey matter reductions (including bilateral anterior cingulate gyrus, left insula and left fusiform gyrus) were evident in affective psychosis but not in schizophrenia, although patients with schizophrenia displayed decreased hippocampal grey matter and increased striatal grey matter at a more liberal statistical threshold. Conclusions: Both schizophrenia and affective psychosis are associated with volumetric abnormalities at the onset of frank psychosis, with some of these evident in common brain areas

Vision and Foraging in Cormorants: More like Herons than Hawks?

Background Great cormorants (Phalacrocorax carbo L.) show the highest known foraging yield for a marine predator and they are often perceived to be in conflict with human economic interests. They are generally regarded as visually-guided, pursuit-dive foragers, so it would be expected that cormorants have excellent vision much like aerial predators, such as hawks which detect and pursue prey from a distance. Indeed cormorant eyes appear to show some specific adaptations to the amphibious life style. They are reported to have a highly pliable lens and powerful intraocular muscles which are thought to accommodate for the loss of corneal refractive power that accompanies immersion and ensures a well focussed image on the retina. However, nothing is known of the visual performance of these birds and how this might influence their prey capture technique. Methodology/Principal Findings We measured the aquatic visual acuity of great cormorants under a range of viewing conditions (illuminance, target contrast, viewing distance) and found it to be unexpectedly poor. Cormorant visual acuity under a range of viewing conditions is in fact comparable to unaided humans under water, and very inferior to that of aerial predators. We present a prey detectability model based upon the known acuity of cormorants at different illuminances, target contrasts and viewing distances. This shows that cormorants are able to detect individual prey only at close range (less than 1 m). Conclusions/Significance We conclude that cormorants are not the aquatic equivalent of hawks. Their efficient hunting involves the use of specialised foraging techniques which employ brief short-distance pursuit and/or rapid neck extension to capture prey that is visually detected or flushed only at short range. This technique appears to be driven proximately by the cormorant's limited visual capacities, and is analogous to the foraging techniques employed by herons